Trends in Invasive Interventions and Risk Factors for Early Critical Events in Multiple System Atrophy

Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder involving autonomic failure, cerebellar ataxia, and parkinsonism. Patients often require invasive interventions, such as gastrostomy or tracheostomy, and sudden death is common. This study aimed to elucidate patterns of invasive treatment and identify risk factors for tracheostomy or sudden death within 5 years of onset. In total, 214 patients diagnosed with MSA between November 2014 and October 2024 across 66 institutions in Hokkaido were enrolled in the Hokkaido Rare Disease Consortium for MSA (HoRC-MSA). Patients were grouped by clinical course and interventions. We analyzed use of invasive procedures, including enteral nutrition via gastrostomy, enterostomy, esophagostomy, nasogastric tube insertion, central venous nutrition, tracheostomy, and ventilator support. Multivariable analyses were performed to compare patients with and without early critical events, defined as tracheostomy or sudden death within 5 years of disease onset. Invasive procedures were performed in 63.1% of patients. Patients receiving enteral nutrition and tracheostomy had prolonged survival. Early events correlated with older onset age (mean, 65.9 years), orthostatic hypotension, stridor, and an elevated apnea-hypopnea index (median, 32.45). Patients with preserved activities of daily living (ADL) in the Unified MSA Rating Scale part Ⅳ also had an increased risk of early critical events. Autonomic dysfunction, sleep-disordered breathing, and vocal cord impairment predict key risk factors for early mortality in patients with MSA. Monitoring is necessary, regardless of preserved ADL. The impact of invasive interventions on quality of life should be further explored.